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Plasma p-tau217 and Aβ42/40 as markers of Aβ pathology in the Lewy body continuum
Kyung Ah Woo1,2,3, Eun Jin Yoon4,5, Ryul Kim6
1Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Introduction:
This study evaluated whether plasma phosphorylated tau-217 (p-tau217), amyloid beta (Aβ)42/40, and their combination could serve as biomarkers of Aβ co-pathology across the Lewy body continuum, where Aβ is frequently observed from prodromal to symptomatic stages.
Methods:
Individuals with dementia with Lewy bodies (DLB), Parkinson's disease (PD), and their shared prodromal stage, isolated rapid eye movement (REM) sleep behavior disorder (iRBD) underwent plasma sampling, Aβ-PET, and cognitive testing.
Results:
Higher plasma p-tau217, lower Aβ42/40, and their interaction were associated with greater Aβ-PET uptake. Individuals with higher-than-median p-tau217 and lower-than-median Aβ42/40 showed the highest Aβ burden. Both biomarkers predicted Aβ-PET positivity, but only p-tau217 correlated with cognition. Among 44 iRBD participants followed prospectively, elevated baseline p-tau217 predicted phenoconversion to overt Lewy body disease.
Discussion:
Plasma p-tau217 and Aβ42/40 may serve as accessible biomarkers of cerebral Aβ pathology and help identify individuals across the Lewy body continuum who could benefit from Aβ-targeted therapy.
Highlights:
Plasma phosphorylated tau-217 (p-tau217) and amyloid beta (Aβ)42/40 predict cerebral Aβ burden in the Lewy body continuum. Both biomarkers individually show high accuracy for identifying Aβ positron emission tomography positivity. Plasma p-tau217, but not Aβ42/40, is associated with cognitive performance. Elevated plasma p-tau217 predicts future phenoconversion in isolated rapid eye movement sleep behavior disorder.
